Regulatory variants play important roles in disease susceptibility. Results from genome-wide association have identified many DNA variants that are associated with diseases. However, how these variants influence disease susceptibility is largely unknown. Some of these variants regulate gene expression but the target genes of these regulatory variants have yet to be identified. A challenge is to decide the relevant cell types/ tissues for functional analyses. In human studies, many cell types are not readily available for experimentation. Thus, the knowledge of cell type specificities in gene regulation is important. If many genes are widely expressed and their regulations are similar across multiple cell types, then one can use readily available tissues for functional studies, and expect the results to generalize. In this R21 project, our goal is to determine the number (and identity) of genes that are widely expressed in the human genome, and the extent to which their expression is shared across cell types. We will also examine whether regulatory variants of widely expressed genes are susceptibility variants for human traits and diseases. The specific aims are: 1) identify genes that are expressed across multiple tissues and conditions by in silico analysis of gene expression data in public repositories and deep sequencing, 2) compare regulation of genes that are expressed across different human cells by network analysis and gene mapping studies, and 3) determine whether regulatory variants identified in Aim 2 are susceptibility alleles for common complex diseases. The findings will guide functional studies to identify the regulatory roles of disease susceptibility variants. The results will also provide examples of disease susceptibility alleles that influence expression levels of human genes. Numerous studies have identified DNA sequences that influence a person's risk of developing diseases. An important next step is to study how these DNA sequences affect disease development. Human studies are difficult because many cell types are not available for experimental manipulations. Our study is designed to establish whether regulatory functions are shared among different cells. The results will help to determine whether easily accessible cells such as blood and skin cells can be used as proxies to examine the biological functions of DNA sequences that influence disease risks.